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Rhu-pGSN for Severe Covid-19 Pneumonia

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ClinicalTrials.gov Identifier: NCT04358406
Recruitment Status : Active, not recruiting
First Posted : April 24, 2020
Last Update Posted : March 16, 2021
Sponsor:
Information provided by (Responsible Party):
BioAegis Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE April 16, 2020
First Posted Date  ICMJE April 24, 2020
Last Update Posted Date March 16, 2021
Actual Study Start Date  ICMJE July 30, 2020
Estimated Primary Completion Date May 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 21, 2020)
  • Efficacy: Proportion of subjects alive not on vasopressors, mechanical ventilator, and dialysis [ Time Frame: Day 14 ]
    Proportion of subjects alive not on vasopressors, mechanical ventilator, and dialysis
  • Safety and Tolerability: Proportion of subjects with serious adverse events (SAEs) [ Time Frame: Continuous through Day 28 ]
    Proportion of subjects with SAEs as judged by the investigator
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2020)
  • Efficacy: Daily change in the WHO 9-point severity score [ Time Frame: Daily through at least Day 14 ]
    Daily change in the 9-point Severity Score (ordinal scale) proposed by a special WHO committee for COVID-19 pneumonia where a score of 8 indicates death and 0 is no clinical or virological evidence of COVID-19 infection
  • Efficacy: All cause mortality rate at Days 28 and 90 [ Time Frame: At Days 28 and 90 ]
    All cause mortality rate using Kaplan-Meier survival analysis
  • Efficacy: Proportion of subjects alive without the ongoing use of vasopressors, ongoing intubation/mechanical ventilation, ongoing residence in an intensive care unit (ICU), new ongoing need for dialysis/renal replacement therapy [ Time Frame: Days 7, 28, 60, and 90 ]
    Proportion of subjects alive without the ongoing use of vasopressors, ongoing intubation/mechanical ventilation, ongoing residence in an intensive care unit, new ongoing need for dialysis/renal replacement therapy
  • Efficacy: Proportion of subjects discharged to home or immediate prior residence [ Time Frame: Continuous through Day 28 ]
    Proportion of subjects discharged to home or immediate prior residence
  • Efficacy: Length of stay (LOS) of surviving subjects in the hospital and in ICU [ Time Frame: Continuous through day 28 ]
    LOS of surviving subjects in the hospital and in ICU
  • Efficacy: Proportion of subjects readmitted to the hospital [ Time Frame: Up to 90 days ]
    Proportion of subjects readmitted to the hospital
  • Safety and Tolerability: Proportion of subjects with adverse events (AEs) [ Time Frame: Continuous through Day 28 ]
    Proportion of subjects with adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
  • Safety and Tolerability: Proportion of subjects with new or worsening clinically significant laboratory abnormalities [ Time Frame: Continuous through Day 28 ]
    Proportion of subjects with new or worsening clinically significant laboratory abnormalities
  • Immunogenicity: Proportion of subjects with rhu-pGSN antibodies [ Time Frame: Days 1, 28, and 90 ]
    Proportion of subjects with rhu-pGSN antibodies
  • Pharmacokinetics: Maximum concentration (C max) of added rhu-pGSN [ Time Frame: Continuous through day 3 ]
    Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial).
  • Pharmacokinetics: Time to maximum concentration (T max) of added rhu-pGSN [ Time Frame: Continuous through day 3 ]
    Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial).
  • Pharmacokinetics: Half-life (T 1/2) of added rhu-pGSN [ Time Frame: Continuous through day 3 ]
    Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)
  • Pharmacokinetics: Area under the curve from time 0 to 8 hours (AUC 0-8) of added rhu-pGSN [ Time Frame: Continuous through day 3 ]
    Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)
  • Pharmacokinetics: Area under the curve from time 0 to infinity (AUC 0-inf) of added rhu-pGSN [ Time Frame: Continuous through day 3 ]
    Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)
Original Secondary Outcome Measures  ICMJE
 (submitted: April 21, 2020)
  • Efficacy: All cause mortality rate though Day 28 [ Time Frame: Continuous through Day 28 ]
    All cause mortality rate using Kaplan-Meier survival analysis
  • Efficacy: Change in World Health Organisation (WHO) 9-point severity score [ Time Frame: Daily through at least Day 14 ]
    Change in the 9-point Severity Score (ordinal scale) proposed by a special WHO committee for COVID-19 pneumonia where a score of 8 indicates death and 0 is no clinical or virological evidence of COVID-19 infection
  • Efficacy: Proportion of subjects discharged to home or immediate prior residence [ Time Frame: Continuous through Day 28 ]
    Proportion of subjects discharged to home or immediate prior residence
  • Efficacy: Number of days alive and off the ventilator [ Time Frame: Continuous through Day 28 ]
    Number of days alive and off the ventilator
  • Efficacy: Length of stay (LOS) of surviving subjects in the hospital [ Time Frame: Continous through day 28 ]
    LOS in hospital (days) of surviving subjects
  • Efficacy: Proportion of subjects readmitted to the hospital [ Time Frame: Up to 90 days ]
    Proportion of subjects readmitted to the hospital
  • Safety and Tolerability: Proportion of subjects with Grade 3-4 clinically significant laboratory abnormalities. [ Time Frame: Continuous through Day 28 ]
    Clinically significant laboratory abnormalities graded according to the National Cancer Institute (NCI) as follows: Grade 0: No abnormalities, Grade 3: Moderate, Grade 4:Severe
  • Safety and Tolerability: Proportion of subjects with non-serious adverse events (AEs) [ Time Frame: Continuous through Day 28 ]
    Proportion of subjects with non-serious adverse events (AEs)
  • Immunogenicity: Proportion of subjects with anti-pGSN antibodies [ Time Frame: Days 0, 28, and 90 ]
    Proportion of subjects with anti-pGSN antibodies
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rhu-pGSN for Severe Covid-19 Pneumonia
Official Title  ICMJE A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Proof-Of-Concept Study To Evaluate Efficacy And Safety Of Recombinant Human Plasma Gelsolin (Rhu-pGSN) Added To Standard Of Care In Subjects With Severe Covid-19 Pneumonia
Brief Summary

Study Objectives:

Primary

  • To assess the efficacy (survival without organ failure on Day 14) of three doses of rhu-pGSN administered intravenously (IV) plus standard of care (SOC) to hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5 or 6 on the World Health Organization (WHO) 9-point severity scale
  • To evaluate the safety and tolerability of three IV doses of rhu-pGSN administered to hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5, or 6 on the WHO 9-point severity scale

Secondary

  • To further assess the efficacy of IV administered rhu-pGSN
  • To assess changes in WHO 9-point severity score for SOC with or without rhu-pGSN
  • To evaluate the effect of administered rhu-pGSN on survival rates
  • To assess the relationship of pGSN levels (and other biomarkers) at baseline with clinical outcomes
  • [OPTIONAL] To follow the pharmacokinetics (PK) of administered rhu-pGSN

Immunogenicity

• To investigate the development of antibodies against rhu-pGSN post-treatment

Detailed Description

Efficacy and safety of IV rhu-pGSN on top of SOC will be evaluated initially in 60 participants representative of the drug target population: high-risk subjects with acute severe pneumonia due to COVID-19. The rhu-pGSN dose will be based on actual body weight given at 12 mg/kg. Three doses will be given at 0, 12 and 24 hours intervals promptly after enrollment by IV infusion through a 0.2 µm filter. Participants will be randomized 1:1 rhu-pGSN or placebo. Interim safety analyses will be conducted after enrollment of 12, 24, 36, and 48 patients.

The primary efficacy outcome will be the proportion of patients surviving on Day 14 without mechanical ventilation, vasopressors or dialysis. Secondary efficacy outcomes will include: daily change in 9-point WHO severity score through at least Day 14; all-cause mortality at Days 28 and 90; time to death (Kaplan-Meier survival analysis); proportion of subjects alive on Days 7, 28, 60, and 90 without: ongoing use of vasopressors, ongoing intubation/mechanical ventilation, ongoing residence in an intensive care unit (ICU), new ongoing need for dialysis/renal replacement therapy; proportion of subjects discharged to home or immediate prior residence by Day 28; days on the ventilator; length of stay in hospital and in ICU and re-admission to an acute-care hospital up to Day 90. Safety of administration of rhu-pGSN at the indicated dosage will also be evaluated.

Baseline and sequential levels of pGSN and inflammatory biomarkers will be measured. On days 1, 28, and 90, immunogenicity due to the formation of anti-pGSN antibodies will be assessed.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
Randomized, blinded, placebo controlled interventional
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Treatment blinded to all but unblinded pharmacist
Primary Purpose: Treatment
Condition  ICMJE Sars-CoV2
Intervention  ICMJE
  • Drug: Recombinant human plasma gelsolin (Rhu-pGSN)
    Intravenous administration of rhu-pGSN at 12 mg/kg, 3 doses
    Other Name: gelsolin
  • Other: Placebo
    Normal saline in matched volume to treatment arm. Undistinguishable in syringe.
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Normal saline in matched volume to treatment arm. Undistinguishable in syringe.
    Intervention: Other: Placebo
  • Active Comparator: Rhu-pGSN
    Recombinant human plasma gelsolin reconstituted for slow bolus injection.
    Intervention: Drug: Recombinant human plasma gelsolin (Rhu-pGSN)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 21, 2020)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2021
Estimated Primary Completion Date May 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Hospitalized with laboratory-confirmed (RT-PCR+) or highly suspected (compatible with at least bilobar lung involvement without another plausible diagnosis) COVID-19
  • Weight ≤100 kg
  • Within 24 hours of reaching a WHO severity score of 4-6 either:

    • At admission
    • While already hospitalized
  • Informed consent obtained from subject/next of kin/legal proxy
  • Primary admitting diagnosis of pneumonia supported by a compatible clinical presentation with a documented infiltrate consistent with pneumonia on chest radiograph or CT as assessed by the admitting emergency-department (ED), clinic, or ward physician or equivalent caregiver
  • Recommended (not mandatory) guidance/discretionary criteria defining patients with pneumonia satisfying all 4 categories below:

    • At least 2 symptoms: difficulty breathing, cough, production of purulent sputum, or chest pain
    • At least 2 vital sign abnormalities: fever, tachycardia, or tachypnea (thresholds -- fever: oral or core temperature >100.4 °F [38 °C]; heart rate >100 beats/min; respiratory rate >24/min)
    • At least one finding of other clinical signs and laboratory abnormalities: hypoxemia (O2 saturation <90%), clinical evidence of pulmonary consolidation, or leukocytosis or leukopenia
    • Chest imaging or CT showing new (or presumed new or worsening) pulmonary infiltrates

      • Principal investigator to note radiologic findings in the electronic case report form (eCRF)
      • Radiology report to be placed in the eCRF
      • A copy of the radiograph attached to be saved for review
  • A hyperinflammatory status (defined by increased ferritin ≥500 µg/L, D-dimer ≥1000 ng/mL, or C-reactive protein (CRP) ≥75 mg/L)
  • During the course of the study starting at screening and for at least 6 months after their final study treatment:

    • Female subjects of childbearing potential must agree to use 2 medically accepted birth control methods
    • Male subjects with a partner who might become pregnant must agree to use reliable forms of contraception (i.e., vasectomy, abstinence), or an acceptable method of birth control must be used by the partner
    • All subjects must agree not to donate sperm or eggs (ovocytes)

Exclusion Criteria:

  • A negative RT-PCR test for COVID-19 during the evaluation of the present illness
  • Extracorporeal membrane oxygenation (ECMO)
  • Pregnant or lactating women
  • Active underlying cancer treated with systemic chemotherapy or radiation therapy during the last 30 days
  • Transplantation of hematopoietic or solid organs
  • Chronic mechanical ventilation or dialysis
  • Otherwise unsuitable for study participation because of chronic, severe, end-stage, and life-limiting underlying disease unrelated to COVID-19 likely to interfere with management and assessment of acute pneumonia, only comfort or limited (non-aggressive) care is to be given, or life expectancy <6 months unrelated to acute COVID infection in the opinion of the Investigator
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Romania,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04358406
Other Study ID Numbers  ICMJE BTI-202
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party BioAegis Therapeutics Inc.
Study Sponsor  ICMJE BioAegis Therapeutics Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Mark J DiNubile, MD BioAegis Therapeutics Inc.
PRS Account BioAegis Therapeutics Inc.
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP